The proposed research is a kinetic investigation of the mechanisms of conformational transformations of proteins, nucleic acids, and phospholipid model membranes. Since these processes may proceed through a multitude of states closely spaced in free energy or else may be highly cooperative, it is important to measure the kinetics of response to the smallest possible perturbations consistent with precise measurement. This should elicit a response which reflects the properties of the least possible number of intermediate states and should simplify the behavior of highly cooperative systems. An apparatus using small pressure perturbations to study conformational dynamics has been constructed and proved in several types of applications. Optical and conductometric methods are used to monitor the progress of the conformational transitions. The apparatus and methods will be further simplified and improved and will be applied to study the following phenomena: (1) folding of proteins. Currently this phase of the project is focused on the folding of cytochrome c as measured by repetitive pressure perturbation (RPP) kinetics using the absorption of visible light by the heme to indicate reaction progress. The kinetics of folding at various temperatures, pH, and urea concentrations will be studied. (2) the gel-liquid crystal transformation in phospholipid bilayer vesicles. RPP kinetics of the transition using 90 degree light scattering to detect reaction progress are being measured. The dependence of the kinetics on temperature and the size and concentration of the vesicles will be studied.